PROJECT-005: TRANSLATIONAL THERAPEUTICS PROGRAM (TT) PROJECT SUMMARY / ABSTRACT The Translational Therapeutics Program at The Ohio State University Comprehensive Cancer Center (OSUCCC), led by David Carbone, MD, PhD and Denis Guttridge, PhD, unites an outstanding team of 55 basic, translational and/or clinical researchers from 17 departments within the Colleges of Business, Medicine, Engineering, Pharmacy, and Veterinary Medicine at Ohio State University. This Program is a continuation of the 15 year-old Experimental Therapeutics (ET) Program that included both liquid and solid tumors. However, as the result of a strategic effort to grow the solid tumor presence in the OSUCCC, we successfully recruited an additional 38 solid tumor physicians, basic scientists, and physician-scientists during this last funding cycle, 16 of who came into the ET Program. We also transitioned to new leadership in the departments of radiation oncology and pathology, as well as in the divisions of medical oncology, surgical oncology and gynecologic oncology, each with expertise in translational medicine and each a member of this Program. With more emphasis on translation and less emphasis on experimental pharmacology, we renamed the ET Program ?Translational Therapeutics (TT)?. Under the leadership of Drs. Carbone and Guttridge the TT Program has seen significant progress during the last cycle, producing 874 peer-reviewed publications among which 9% are in high impact (>10) journals, 28% from intra-programmatic collaborations, 43% from inter-programmatic collaborations; 59% are multi-institutional and 86% are collaborative publications. TT Program members have collaborated on programmatic grant submissions and have been awarded 2 NCI P01s, a U01, a U54 SPORE, and a U10 programmatic grant focused on solid tumor biology, as well as two T32 training grants. As a consequence of these and other collaborative efforts, the TT Program has $8.8M in current annual direct costs from peer-reviewed grants of which $7.3M (83%) is from the NCI. The TT Program is well-integrated with the clinical teams via participation in the multidisciplinary Disease Specific Research Groups. As such, there were 5,253 accruals to interventional clinical trials during the last funding cycle of which 4,357 (83%) were therapeutic; 2043 (47%) of the latter resulted from investigator-initiated clinical trials. The overall goal of the TT Program is to pursue solid tumor biology in order to develop and translate promising preclinical studies into innovative clinical trials for the successful prevention, diagnosis and treatment of solid tumors. This goal will be achieved by performing the following specific aims: 1) Identifying alterations in solid tumor signaling pathways to develop targeted therapeutics; 2) Identifying and therapeutically targeting tumor-host interactions; and 3) Improving upon or developing new approaches for determining prognosis, selecting appropriate therapy and evaluating the response to treatment. Future directions include continued strategic recruitments and heavy leveraging of the OSUCCC's Drug Development Institute (DDI) to move a number of our exciting compounds in the TT Program into the clinic for a variety of solid tumors.